Degree of Cajal-Retzius cell mislocalisation correlates with the severity of structural brain defects in mouse models of dystroglycanopathy

The secondary dystroglycanopathies are characterized by the hypoglycosylation of alpha dystroglycan, and are associated with mutations in at least 18 genes that act on the glycosylation of this cell surface receptor rather than the Dag1 gene itself. At the severe end of the disease spectrum, there are substantial structural brain defects, the most striking of which is often cobblestone lissencephaly. The aim of this study was to determine the gene‐specific aspects of the dystroglycanopathy brain phenotype through a detailed investigation of the structural brain defects present at birth in three mouse models of dystroglycanopathy—the FKRPKD, which has an 80% reduction in Fkrp transcript levels; the Pomgnt1null, which carries a deletion of exons 7–16 of the Pomgnt1 gene; and the Largemyd mouse, which carries a deletion of exons 5–7 of the Large gene. We show a rostrocaudal and mediolateral gradient in the severity of brain lesions in FKRPKD, and to a lesser extent Pomgnt1null mice. Furthermore, the mislocalization of Cajal–Retzius cells is correlated with the gradient of these lesions and the severity of the brain phenotype in these models. Overall these observations implicate gene‐specific differences in the pathogenesis of brain lesions in this group of disorders

Gridded and direct Epoch of Reionisation bispectrum estimates using the Murchison Widefield Array

We apply two methods to estimate the 21~cm bispectrum from data taken within the Epoch of Reionisation (EoR) project of the Murchison Widefield Array (MWA). Using data acquired with the Phase II compact array allows a direct bispectrum estimate to be undertaken on the multiple redundantly-spaced triangles of antenna tiles, as well as an estimate based on data gridded to the $uv$-plane. The direct and gridded bispectrum estimators are applied to 21 hours of high-band (167--197~MHz; $z$=6.2--7.5) data from the 2016 and 2017 observing seasons. Analytic predictions for the bispectrum bias and variance for point source foregrounds are derived. We compare the output of these approaches, the foreground contribution to the signal, and future prospects for measuring the bispectra with redundant and non-redundant arrays. We find that some triangle configurations yield bispectrum estimates that are consistent with the expected noise level after 10 hours, while equilateral configurations are strongly foreground-dominated. Careful choice of triangle configurations may be made to reduce foreground bias that hinders power spectrum estimators, and the 21~cm bispectrum may be accessible in less time than the 21~cm power spectrum for some wave modes, with detections in hundreds of hours.Comment: 19 pages, 10 figures, accepted for publication in PAS

Transgenic Rescue of the LARGEmyd Mouse: A LARGE Therapeutic Window?

LARGE is a glycosyltransferase involved in glycosylation of α-dystroglycan (α-DG). Absence of this protein in the LARGEmyd mouse results in α-DG hypoglycosylation, and is associated with central nervous system abnormalities and progressive muscular dystrophy. Up-regulation of LARGE has previously been proposed as a therapy for the secondary dystroglycanopathies: overexpression in cells compensates for defects in multiple dystroglycanopathy genes. Counterintuitively, LARGE overexpression in an FKRP-deficient mouse exacerbates pathology, suggesting that modulation of α-DG glycosylation requires further investigation. Here we demonstrate that transgenic expression of human LARGE (LARGE-LV5) in the LARGEmyd mouse restores α-DG glycosylation (with marked hyperglycosylation in muscle) and that this corrects both the muscle pathology and brain architecture. By quantitative analyses of LARGE transcripts we also here show that levels of transgenic and endogenous LARGE in the brains of transgenic animals are comparable, but that the transgene is markedly overexpressed in heart and particularly skeletal muscle (20–100 fold over endogenous). Our data suggest LARGE overexpression may only be deleterious under a forced regenerative context, such as that resulting from a reduction in FKRP: in the absence of such a defect we show that systemic expression of LARGE can indeed act therapeutically, and that even dramatic LARGE overexpression is well-tolerated in heart and skeletal muscle. Moreover, correction of LARGEmyd brain pathology with only moderate, near-physiological LARGE expression suggests a generous therapeutic window

The Phase II Murchison Widefield Array: Design overview

We describe the motivation and design details of the "Phase II" upgrade of the Murchison Widefield Array (MWA) radio telescope. The expansion doubles to 256 the number of antenna tiles deployed in the array. The new antenna tiles enhance the capabilities of the MWA in several key science areas. Seventy-two of the new tiles are deployed in a regular configuration near the existing MWA core. These new tiles enhance the surface brightness sensitivity of the MWA and will improve the ability of the MWA to estimate the slope of the Epoch of Reionisation power spectrum by a factor of ~3.5. The remaining 56 tiles are deployed on long baselines, doubling the maximum baseline of the array and improving the array u,v coverage. The improved imaging capabilities will provide an order of magnitude improvement in the noise floor of MWA continuum images. The upgrade retains all of the features that have underpinned the MWA's success (large field-of-view, snapshot image quality, pointing agility) and boosts the scientific potential with enhanced imaging capabilities and by enabling new calibration strategies

A Survey of Kiloparsec-Scale Radio Outflows in Radio-Quiet Active Galactic Nuclei

Seyfert galaxies commonly host compact jets spanning 10-100 pc scales, but larger structures (KSRs) are resolved out in long baseline, aperture synthesis surveys. We report a new, short baseline Very Large Array (VLA) survey of a complete sample of Seyfert and LINER galaxies. Out of all of the surveyed radio-quiet sources, we find that 44% (19 / 43) show extended radio structures at least 1 kpc in total extent that do not match the morphology of the disk or its associated star-forming regions. The KSR Seyferts stand out by deviating significantly from the far-infrared - radio correlation for star-forming galaxies, and they are more likely to have a relatively luminous, compact radio source in the nucleus; these results argue that KSRs are powered by the AGN rather than starburst. KSRs probably originate from jet plasma that has been decelerated by interaction with the nuclear ISM. We demonstrate the jet loses virtually all of its power to the ISM within the inner kiloparsec to form the slow KSRs.Comment: to appear in the Astronomical Journal, Vol 132 (projected

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

The aperture array verification system 1 : system overview and early commissioning results

The design and development process for the Square Kilometre Array (SKA) radio telescope’s Low Frequency Aperture Array component was progressed during the SKA pre-construction phase by an international consortium, with the goal of meeting requirements for a critical design review. As part of the development process a full-sized prototype SKA Low ‘station’ was deployed – the Aperture Array Verification System 1 (AAVS1). We provide a system overview and describe the commissioning results of AAVS1, which is a low frequency radio telescope with 256 dual-polarisation log-periodic dipole antennas working as a phased-array. A detailed system description is provided, including an in-depth overview of relevant sub-systems, ranging from hardware, firmware/software, calibration and control sub-systems. Early commissioning results cover initial bootstrapping, array calibration, stability testing, beamforming and on-sky sensitivity validation. Lessons learned are presented, as well as future developments.peer-reviewe

Follow up of GW170817 and its electromagnetic counterpart by Australian-led observing programmes

The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor